19-46660910-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_145056.3(DACT3):ā€‹c.155T>Cā€‹(p.Met52Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000268 in 1,494,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000067 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000022 ( 0 hom. )

Consequence

DACT3
NM_145056.3 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.944
Variant links:
Genes affected
DACT3 (HGNC:30745): (dishevelled binding antagonist of beta catenin 3) Predicted to enable delta-catenin binding activity; protein kinase A binding activity; and protein kinase C binding activity. Involved in negative regulation of canonical Wnt signaling pathway and negative regulation of cell growth. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]
DACT3-AS1 (HGNC:44120): (DACT3 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.068185896).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DACT3NM_145056.3 linkuse as main transcriptc.155T>C p.Met52Thr missense_variant 1/4 ENST00000391916.7 NP_659493.2
DACT3-AS1NR_040042.1 linkuse as main transcriptn.45+502A>G intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DACT3ENST00000391916.7 linkuse as main transcriptc.155T>C p.Met52Thr missense_variant 1/45 NM_145056.3 ENSP00000375783 P1
DACT3ENST00000410105.2 linkuse as main transcriptc.155T>C p.Met52Thr missense_variant 1/32 ENSP00000387300
DACT3-AS1ENST00000525008.5 linkuse as main transcriptn.45+502A>G intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.00000667
AC:
1
AN:
149820
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000208
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000227
AC:
3
AN:
131924
Hom.:
0
AF XY:
0.0000138
AC XY:
1
AN XY:
72274
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000296
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000223
AC:
3
AN:
1344324
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
663978
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000932
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000667
AC:
1
AN:
149820
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
73116
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000208
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsNov 09, 2023The c.155T>C (p.M52T) alteration is located in exon 1 (coding exon 1) of the DACT3 gene. This alteration results from a T to C substitution at nucleotide position 155, causing the methionine (M) at amino acid position 52 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.35
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
19
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0051
T;.
Eigen
Benign
-0.52
Eigen_PC
Benign
-0.39
FATHMM_MKL
Benign
0.52
D
LIST_S2
Benign
0.43
T;T
M_CAP
Uncertain
0.26
D
MetaRNN
Benign
0.068
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.69
N;.
MutationTaster
Benign
0.91
N;N
PrimateAI
Pathogenic
0.92
D
PROVEAN
Benign
-0.26
N;N
REVEL
Benign
0.052
Sift
Benign
0.43
T;D
Sift4G
Benign
0.46
T;D
Polyphen
0.89
P;B
Vest4
0.25
MutPred
0.25
Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);
MVP
0.39
ClinPred
0.14
T
GERP RS
1.9
Varity_R
0.037
gMVP
0.11

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1360404453; hg19: chr19-47164167; API